A Prospective, Open, Single-arm Phase II Clinical Study to Evaluate the Efficacy and Safety of Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma.
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- PD-1 Antibody
- Sponsor
- China Medical University, China
- Enrollment
- 1
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective, open, single-arm Phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody combined with autologous DC and NK cells in the treatment of digestive carcinoma.
Detailed Description
This is a prospective, open, single-arm Phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody combined with autologous DC and NK cells in the treatment of digestive carcinoma. This project aims to enhance the anti-tumour activity of DC/NK cells in combination with anti-PD-1 antibodies, and ultimately activate the patient's own immune function to improve the quality of life and survival time of tumour patients, and provide objective evidence for the widespread use of targeted immune cell therapy in the clinical setting.
Investigators
Yunpeng Liu
Director of Department of Medical Oncology
China Medical University, China
Eligibility Criteria
Inclusion Criteria
- •age: 18-70 years, of either sex
- •pathologically confirmed locally advanced or metastatic gastrointestinal tumour (stage III or IV according to AJCC 8th edition staging) with at least one measurable lesion (meeting RECIST 1.1 criteria)
- •ECOG PS: 0-1 points
- •have adequate organ and bone marrow function, i.e. meet the following criteria.
- •Routine blood test criteria to be met.
- •HB ≥ 90g/L.
- •ANC ≥1.5×109/L.
- •PLT ≥90 x 109/L.
- •Absolute value of lymphocytes + monocytes \>2.0\*10\^9/L.
- •Biochemical tests are required to meet the following criteria.
Exclusion Criteria
- •known hypersensitivity to any of the components of the anti-PD-1 antibody formulation; or previous severe allergic reactions to other monoclonal antibodies.
- •diagnosis of other malignancies, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radically resected carcinoma in situ, within 5 years prior to the first dose
- •Subjects who have been treated with an antitumour vaccine or other antitumour agents with immunostimulatory effects (interferon, interleukin, thymidine, immune cell therapy, etc.) within 1 month prior to the first dose.
- •CNS metastases with symptoms. Subjects may be enrolled in the study if their CNS metastases have been treated, e.g., clinical stability (MRI detection) has been maintained for at least 4 weeks, and the subject's clinical symptoms, such as neurological symptoms, are able to return to baseline levels at least 2 weeks prior to the first dose (except for residual signs or symptoms related to CNS treatment). In addition, subjects receiving stable or tapered doses of ≤10 mg/day of prednisone (or equivalent) for at least 2 weeks for clinical symptoms associated with treatment with corticosteroids are not eligible for enrollment in the study, otherwise they cannot be enrolled.
- •Acute or chronic active hepatitis B (defined as positive HBsAg for hepatitis B virus surface antigen at screening) or hepatitis C infection. Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as hepatitis B core (HBc) antibody positive and HBsAg negative) who are negative for HBV DNA only may be enrolled in this study. HBV DNA testing must be performed on this group of patients prior to enrolment. Patients who are positive for hepatitis C virus (HCV) antibodies and negative for HCV RNA only by polymerase chain reaction may be enrolled in the study. Patients who are antigen-positive but have DNA/RNA copy numbers within the permissible range should be considered for antiviral treatment if enrolled in this study and DNA/RNA levels should be monitored in real time for the duration of the study.
- •previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases.
- •active tuberculosis (TB), on anti-TB treatment or who have received anti-TB treatment within 1 year prior to the first dose
- •Human immunodeficiency virus (HIV) infected (HIV-positive), known syphilis infection
- •Patients who are considered to be at high medical risk due to severe, uncontrollable disease, non-metastatic systemic disease or having an active, uncontrollable infection. Some examples include, but not all, uncontrolled ventricular arrhythmias, recent (within 3 months) myocardial infarction, uncontrollable grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, HRCT suggestive of extensive bilateral interstitial lung disease or any mental illness that may prevent informed consent from being obtained
- •active autoimmune disease requiring systemic therapy (e.g. use of disease-relieving drugs, corticosteroids or immunosuppressants) that occurred within 2 years prior to the first dose Alternative therapies (e.g. thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are permitted Known history of primary immunodeficiency. Patients with positive autoimmune antibodies only need to confirm the presence of autoimmune disease at the discretion of the investigator.
Arms & Interventions
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Pembrolizumab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Nivolumab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Sintilimab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Toripalimab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Camrelizumab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: Tislelizumab
Anti-PD-1 antibody combined with autologous DC and NK cells
Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.
Intervention: NK-Cell or DC-Cell
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: one year
PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
Secondary Outcomes
- Overall Survival (OS)(two years)
- Objective Response Rate (ORR)(one year)
- Disease Control Rate (DCR)(one year)